ENCePP Guide on Methodological Standards in Pharmacoepidemiology

5.7. Systematic reviews and meta-analysis

There may be results from more
than one study with the same or similar research objective, and identification
and integration of this evidence can extend our understanding of the issue. The
focus of this activity may be to learn from the diversity of designs, results
and associated gaps in knowledge as well as to obtain overall risk estimates. An
example is the meta-analysis of results of individual studies with potentially
different design e.g. Variability in risk of gastrointestinal complications with
individual NSAIDs: results of a collaborative meta-analysis (BMJ
1996;312:1563-6), which compared the relative risks of serious gastrointestinal
complications reported with individual NSAIDs by conducting a systematic review
of twelve hospital and community based case-control and cohort studies, and
found a relation between use of the drugs and admission to hospital for
haemorrhage or perforation.

A systematic literature review
aims to collect all empirical evidence that fits pre-specified eligibility
criteria to answer a specific research question. These reviews use systematic
and explicit methods to identify and critically appraise relevant research, and
to analyse the data included in the review. A meta-analysis involves the use of
statistical techniques to integrate and summarize the results of identified
studies.

Systematic review and
meta-analysis of observational studies and other epidemiological sources are
becoming as common as those of RCTs. Challenges in systematic reviews that assess treatment
harms (Ann Intern Med 2005;142:1090-9) explains the different reasons
why both are important in providing relevant information and knowledge for
pharmacovigilance.

A detailed guidance on the
methodological conduct of systematic reviews and meta-analysis is reported in Annex 1 of this guide. This guidance includes links to
other relevant resources.

It should be noted that
meta-analysis, even of randomised controlled trials, shares characteristics with
observational research: the studies are often produced according to an unplanned
process and subjective processes are involved in selection of studies to
include. Careful planning in design of a meta-analysis and pre-specification of
selection criteria, outcomes and analytical methods before review of any study
results may thus add appreciably to the confidence that is placed in the
results. A further useful reference is the CIOMS Working Group X Guideline on Evidence Synthesis and Meta-Analysis for Drug
Safety (Geneva 2016).